Ten-year incidence of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-seropositive former blood donors

Abstract

Background: Very few studies have measured disease penetrance and prognostic factors of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-infected persons.

Methods and results: We performed a retrospective cohort study among initially healthy blood donors with an index T cruzi-seropositive donation and age-, sex-, and period-matched seronegatives in 1996 to 2002 in the Brazilian cities of São Paulo and Montes Claros. In 2008 to 2010, all subjects underwent medical history, physical examination, ECGs, and echocardiograms. ECG and echocardiogram results were classified by blinded core laboratories, and records with abnormal results were reviewed by a blinded panel of 3 cardiologists who adjudicated the outcome of Chagas cardiomyopathy. Associations with Chagas cardiomyopathy were tested with multivariate logistic regression. Mean follow-up time between index donation and outcome assessment was 10.5 years for the seropositives and 11.1 years for the seronegatives. Among 499 T cruzi seropositives, 120 (24%) had definite Chagas cardiomyopathy, and among 488 T cruzi seronegatives, 24 (5%) had cardiomyopathy, for an incidence difference of 1.85 per 100 person-years attributable to T cruzi infection. Of the 120 seropositives classified as having Chagas cardiomyopathy, only 31 (26%) presented with ejection fraction <50%, and only 11 (9%) were classified as New York Heart Association class II or higher. Chagas cardiomyopathy was associated (P<0.01) with male sex, a history of abnormal ECG, and the presence of an S3 heart sound.

Conclusions: There is a substantial annual incidence of Chagas cardiomyopathy among initially asymptomatic T cruzi-seropositive blood donors, although disease was mild at diagnosis.

Figure 1

Expert panel review criteria. The Retrovirus Epidemiology Donor Study-II (REDS-II) Chagas study protocol included an expert panel review, tasked with determining whether a donor’s cardiac findings were attributable to Chagas disease. Those records meeting the cardiac signs and symptoms trigger algorithm presented here were selected for review by the 3-member expert panel. Only records that had complete clinical examination, ECG, and echocardiography data were eligible for trigger consideration. The Appendix in the online-only Data Supplement gives additional information on how the expert panel designated a person as definite, probable, possible, or not Chagas cardiomyopathy. BSA indicates body surface area; LA, left atrial; LAE, left atrial enlargement; LV, left ventricular; and TR, tricuspid regurgitation.

Figure 2

Donors included and excluded in the Retrovirus Epidemiology Donor Study-II (REDS-II) Chagas study. A total of 1327 seropositive and 1887 seronegative blood donors were recruited for this study. In total, 39% of the seropositives and 27% of the seronegatives enrolled. Ninety-eight percent of the enrolled seropositives and 97% of the enrolled seronegatives had complete clinical, ECG, and echocardiography data and were considered eligible for trigger consideration. Sixty-three percent of the seropositives and 48% of the seronegatives met the trigger criteria, and their cardiac findings were reviewed by the expert panel.